Central role of Prominin-1 in lipid rafts during liver regeneration

Myeong-Suk Bahn, Dong-Min Yu, Myoungwoo Lee, Sung-Je Jo, Ji-Won Lee, Ho-Chul Kim, Hyun Lee, Hong Lim Kim, Arum Kim, Jeong-Ho Hong, Jun Seok Kim, Seung-Hoi Koo, Jae-Seon Lee and Young-Gyu Ko ()
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Myeong-Suk Bahn: Korea University
Dong-Min Yu: Korea University
Myoungwoo Lee: Korea University
Sung-Je Jo: Korea University
Ji-Won Lee: Korea University
Ho-Chul Kim: Korea University
Hyun Lee: Korea University
Hong Lim Kim: Integrative Research Support Center, College of Medicine, The Catholic University of Korea
Arum Kim: Korea University
Jeong-Ho Hong: Korea University
Jun Seok Kim: Korea University
Seung-Hoi Koo: Korea University
Jae-Seon Lee: College of Medicine, Inha University
Young-Gyu Ko: Korea University

Nature Communications, 2022, vol. 13, issue 1, 1-16

Abstract: Abstract Prominin-1, a lipid raft protein, is required for maintaining cancer stem cell properties in hepatocarcinoma cell lines, but its physiological roles in the liver have not been well studied. Here, we investigate the role of Prominin-1 in lipid rafts during liver regeneration and show that expression of Prominin-1 increases after 2/3 partial hepatectomy or CCl4 injection. Hepatocyte proliferation and liver regeneration are attenuated in liver-specific Prominin-1 knockout mice compared to wild-type mice. Detailed mechanistic studies reveal that Prominin-1 interacts with the interleukin-6 signal transducer glycoprotein 130, confining it to lipid rafts so that STAT3 signaling by IL-6 is effectively activated. The overexpression of the glycosylphosphatidylinsositol-anchored first extracellular domain of Prominin-1, which is the domain that binds to GP130, rescued the proliferation of hepatocytes and liver regeneration in liver-specific Prominin-1 knockout mice. In summary, Prominin-1 is upregulated in hepatocytes during liver regeneration where it recruits GP130 into lipid rafts and activates the IL6-GP130-STAT3 axis, suggesting that Prominin-1 might be a promising target for therapeutic applications in liver transplantation.

Date: 2022
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DOI: 10.1038/s41467-022-33969-4

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